Southern African Journal of Anaesthesia and Analgesia. 2020;26(6 Suppl 3):S113-117 https://doi.org/10.36303/SAJAA.2020.26.6.S3.2554 South Afr J Anaesth Analg Open Access article distributed under the terms of the ISSN 2220-1181 EISSN 2220-1173 Creative Commons License [CC BY-NC 3.0] © 2020 The Author(s) http://creativecommons.org/licenses/by-nc/3.0 FCA 1 REFRESHER COURSE A review of common psychedelic drugs S Mayet Department of Anaesthesia, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, South Africa Corresponding author, email: [email protected] Summary Psychedelic substances have traditionally been used in medicine and religious rituals. Their use dates back thousands of years with fossil evidence as old as 10 000 years. Throughout the 1950s and 1960s psychedelics were used in clinical studies. These drugs then saw widespread use in hippie culture and were viewed as a drug of abuse with no medicinal value.1 Currently, psychedelics are being investigated as adjuncts to existing psycho therapeutic approaches including depression and addiction.1 This article will look at definitions, classifications, effects and basic pharmacokinetics and pharmacodynamics of these drugs. In this review I will refer to this group of drugs as psychedelics. Definitions The term psychedelics has been under scrutiny in recent years. Initially, psychedelics were termed hallucinogens, however, we now know that they are not the same.1 Hallucinogens: Refers to a chemical and pharmacological group of substances that cause a distortion in sensory perception of something that does not exist and a mental state resembling psychosis.2 Entactogens: Refers to a class of psychoactive drugs that produce empathy or sympathy and includes emotional openness, oneness and communion with others.1 Psychedelics: Refers to the capacity of a drug to reliably induce states of altered perception, thought and feeling that are not otherwise experienced except in dreams or at times of religious exaltation.1,2 It also refers to the mind-altering substances that have an effect on the conscious experience.2 Entheogens: Refers to newer terminology and is slowly replacing both psychedelics and hallucinogens. It literally means “generat- ing the divine within” but loosely means “non-addictive artificial and natural substances that induce alterations in consciousness.”1 They are a group of substances that induce alterations in perception, mood, consciousness, cognition and behaviour for the purpose of religious or spiritual significance.1 Classification of psychedelic drugs These drugs are classified by the neurotransmitters they mimic. Drug class Cholinergics Entactogens Serotonergics Glutaminergics Opioid kappa receptor agonists Examples • Muscarine • Mescaline • Lysergic Acid Diethylamide • Phencyclidine • Slavinorin A • Scopolamine • Amphetamines (LSD) (PCP) • Myristicin • N,N-Dimethyltryptamine • Ketamine • Elemicin (DMT) • Psilocybin Mechanism • Acts on acetylcholine • 5-Hydroxytryptamine • 5-HT2A agonist • Dissociatives • Acts on opioid of action • Acts on muscarine (5-HT) releasing • Inhibits kappa receptors • Gamma amino • Catecholamine N-methyl-D- • Acts on dopamine butyric acid (GABA) aspartic Acid 2 (D2) receptors agonist (NMDA) Cholinergic psychedelic drugs3,4 Muscarine3 Common examples include Muscarine is a toxic alkaloid found in Amanita muscaria (fly 8 1. Muscarine fungus) and other fungal species like Inocybe. It acts on muscarinic receptors and is an agonist at GABA and is therefore 2. Scopolamine South Afr J Anaesth Analg 2020; 26(6)Supplement S113 http://www.sajaa.co.za A review of common psychedelic drugs neuro depressant.3 Its effects include delirium, salivation, nausea has poor lipid solubility and therefore has poor passage across and diarrhoea, hypotension and shock.3 The antidote is atropine.3 the blood–brain barrier.8 Scopolamine3,4 It is mainly metabolised via the liver and up to 87% is excreted in the urine within 24 hours.8 Also known as deadly nightshade. It is a belladona alkaloid and a muscarinic antagonist that is mainly anticholinergic and has Physiological effects8 psychological effects. Clinically it is used to treat motion sickness, Sympathomimetic activity and mimics noradrenaline and relax smooth muscles and gastric cramping, mild with increasing adrenaline mainly, and effects include: doses, restlessness, confusion, stupor, respiratory depression and coma. • Nausea, vomiting, dizziness, sweating and chills • Dilated pupils Effects3,4 • Dry mouth Parasympathetic effects Dry mouth Pupillary dilation • Anxiety Decreased sweating Smooth muscle relaxation • Ataxia, hyperreflexia Blurred vision Dry skin • Sedation Central nervous system effects 8 Drowsiness Decreased REM sleep Neuropsychiatric effects Mild euphoria Mental confusion • Depersonalisation Amnesia Decreased focus and attention • Complex hallucinations Entactogens (5-HT releasing agents)1,5 • Altered perception especially for colour, sound and shape and for space and time These drugs are catecholamine-like in nature. Examples include • Intact sensorium the phenethylamine mescaline, amphetamines, myristicin and 5 elemicin. Synthetic amphetamines Phenethylamine Methylene-dioxy-methamphetamine (MDMA) is one of the commonest. It is used recreationally.9 Structurally, MDMA is A group of organic compounds which act as a stimulant on the similar to mescaline and resembles adrenaline and noradrenaline. central nervous system. They are used as a dietary supplement Its biological actions are similar to adrenaline, dopamine and and to support mood. They are found occurring in nature, serotonin where it does not act directly on serotonin but rather produced by certain fungi and bacteria and can be found in blocks and binds to serotonin transporter involved in its uptake. chocolates.5 This group of drugs resemble noradrenaline and It is synthetically derived and is also known as a “designer drug”.9 dopamine and probably exhibit their effect by being a HT2A agonist. These drugs are usually ingested orally and metabolised Other street names include “ecstacy”, “XTC”, “ADAM”, “speed”, in the small intestine by monoamine oxidase B (MAO-B) to “Molly”.12 The route of administration includes oral, intravenous, aldehyde dehydrogenase and then to phenylacetic acid.6,7 snorting or adding to drinks (spiking). The dosage varies from 50–150 mg.9 Mescaline 8 Uses9 It is a naturally occurring psychedelic alkaloid of the phene- thylamine derivative. Predominantly used in native America Mainly used recreationally at raves and clubs, MDMA is viewed during religious ceremonies for its mystical properties. It origi- as a fairly safe drug as it is perceived to postpone fatigue and nates from the peyote cactus (Lophophora williamsii) where the cause euphoria. active ingredient is mescaline.8 There is renewed interest for MDMA usage in psychotherapy It is a hallucinogen with psychoactive properties and is 4 000 and trials are currently underway for its use in post-traumatic times less potent than LSD. The dosage range is between stress disorder and for anxiety in the terminally ill and autistic 200–300 mg. The structure of mescaline is similar to serotonin, population. psilocybin and LSD.8 Pharmacokinetics9 Pharmacokinetics MDMA is readily absorbed from the gastrointestinal tract Mescaline is ingested orally and rapidly absorbed within 30 within two hours of oral ingestion. 80% is metabolised via the minutes via the gastrointestinal tract. Its psychedelic effects liver via O-demethylation and N-dealkylation. 20% is excreted are reached within two hours of ingestion and lasts up to eight unchanged in the urine. Slow elimination from the body with hours. The plasma half-life is approximately six hours.8 Mescaline persistence of effects after two days occurs. South Afr J Anaesth Analg 2020; 26(6)Supplement S114 http://www.sajaa.co.za A review of common psychedelic drugs Effects9 O-H-LSD. LSD is eliminated via the urine.11 LSD is still detectable four days post ingestion.11 Short-term 11 Acute adverse effects are usually the result of high or multiple Pharmacodynamics doses. The most serious short-term physical health risks of MDMA LSD is an atypical psychedelic as it has both serotonergic and are hyperthermia and dehydration. Cases of life-threatening or dopaminergic activity. It has mixed affinity for 5-HT1 and 5-HT2 fatal hyponatremia have been reported due to excessive water receptors but mainly 5-HT2 where it increases glutamate levels. intake. Other side effects include bruxism, insomnia, sweating, LSD interacts agonistically and antagonistically at the D1 and D2 diarrhoea, hypertension and tachycardia. Visual and auditory receptors. hallucinations rarely occur. 2,11 Long term9 Effects Psychological effects include depression, impulsiveness, memo- Physical effects include insomnia, decreased appetite, weakness, ry impairment and paranoia. Long-term exposure to MDMA in nausea, temperature changes, tachycardia and hyperreflexia. humans has been shown to produce marked neurodegeneration Psychiatric adverse effects include a “bad trip” that involves in striatal, hippocampal, prefrontal, and occipital serotonergic anxiety, panic, mood swings, flashbacks with hallucinations and axon terminals. feelings of losing control. Overdoses are not directly linked to death, but suicides have been reported. 10 Myristicin and elemicin With repeated administration, there is a decrease in respon- Derivatives include nutmeg and anise. Effects include euphoria, siveness to LSD especially in psychological